2.A.123 The Sweet; PQ-loop; Saliva; MtN3 (Sweet) Family

The eukaryotic proteins of the SWEET family are found in plants, animals, protozoans, bacteria, etc. They have 7 TMSs in a 3+1+3 repeat arrangement. These proteins appear to catalyze facilitated diffusion (entry or export) of sugars across the plant plasma membrane or the endoplasmic reticulum membrane (Takanaga and Frommer, 2010). Plant sweets fall into four subclades (Chen et al., 2010).  The tomato genome encodes 29 SWEETs. Feng et al. 2015 analyzed the structures, conserved domains, and phylogenetic relationships of these proteins, and also analyzed the transcript levels of SWEET genes in various tissues, organs, and developmental stages in response to exogenous sugar and adverse environmental stress (e.g., high and low temperatures). The phylogeny of SWEETS has been described (Jia et al. 2017). A database (dbSWEET) of SWEET homologues is freely available to the scientific community at http://bioinfo.iitk.ac.in/bioinfo/dbSWEET/Home (Gupta and Sankararamakrishnan 2018). SWEETs perform diverse physiological functions in plants such as pollen nutrition, nectar secretion, seed filling, phloem loading, and pathogen nutrition (Jeena et al. 2019). Various SWEETS transport various sugars such as sucrose, fructose, glucose, galactose, and mannose (Hu et al. 2019). SWEETS play important roles in sugar efflux, pollen nutrition, nectar secretion, phloem transport, and seed development (Cao et al. 2019). Identification and expression analysis of the SWEET gene family from Poa pratensis under abiotic Stresses has been published (Zhang et al. 2020). The role of SWEET proteins in fruit development and abiotic stress in pomegranate (Punica granatum) has been reviewed (Kumawat et al. 2022). Garlic (Allium sativum L.) has 27 genes encoding clade I-IV SWEET proteins. The promoters of these genes contained hormone- and stress-sensitive elements associated with plant response to phytopathogens (Filyushin et al. 2023). The HuSWEET Family in Pitaya (Hylocereus undatus) has been identified, and key roles of HuSWEET12a and HuSWEET13d in sugar accumulation have been established (Jiang et al. 2023).  Genome-wide identification and expression analysis of the SWEET gene family in annual alfalfa (Medicago polymorpha) has been achieved (Liu et al. 2023).

On average, angiosperm genomes contain approximately 20 SWEET paralogs, most of which serve distinct physiological roles. In Arabidopsis, AtSWEET8 and 13 feed the pollen; SWEET 11 and 12 provide sucrose to MFS-type sucrose transporters for phloem loading; AtSWEET11, 12 and 15 have distinct roles in seed filling; AtSWEET16 and 17 are vacuolar hexose transporters; and SWEET9 is essential for nectar secretion (Eom et al. 2015). The remaining family members await characterization, and could play roles in the gametophyte and elsewhere in the plant. In rice and cassava, and possibly other systems, sucrose transporting SWEETs play central roles in pathogen resistance. Plant sweets participate in diverse physiological processes, including pathogen nutrition, seed filling, nectar secretion, and phloem loading. There are 28 SWEET genes in tea (Camellia sinensis), and several members from the CsSWEET gene family have been localized and characterized (Jiang et al. 2021). Members of this family have been reported to have the MtN3 fold (Ferrada and Superti-Furga 2022). AtSWEET11 and AtSWEET12 transporters function in tandem to modulate sugar flux in plants (Fatima et al. 2023). SWEET proteins are involved in sugar efflux, phloem loading, reproductive development, plant senescence, and stress responses. There are 23 SWEET transporter encoded within the Medicago polymorpha (alfalfa) genome (Liu et al. 2023), and the transcriptional regulation of several have been determined.

Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Chen et al. (2010) reviewed evidence for a new class of sugar transporters, named SWEETs. At least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.

Plants transport fixed carbon predominantly as sucrose, which is produced in mesophyll cells and imported into phloem cells for translocation throughout the plant. It had not been known how sucrose migrates from sites of synthesis in the mesophyll to the phloem, or which cells mediate efflux into the apoplasm as a prerequisite for phloem loading by the SUT sucrose-H+ (proton) cotransporters. Using optical sucrose sensors, Chen et al. (2012) identified a subfamily of SWEET sucrose efflux transporters. AtSWEET11 and 12 localize to the plasma membrane of the phloem. Mutant plants carrying insertions in AtSWEET11 and 12 are defective in phloem loading, thus revealing a two-step mechanism of SWEET-mediated export from parenchyma cells feeding H+-coupled import into the sieve element-companion cell complex. Restriction of intercellular transport to the interface of adjacent phloem cells may be an effective mechanism to limit the availability of photosynthetic carbon in the leaf apoplasm in order to prevent pathogen infections.

Many bacterial homologues (semisweets) have only 3 TMSs and are half sized, but they nevertheless are members of the MtN3 family with a single 3 TMS repeat unit per polypeptide chain. Other bacterial homologues have 7 TMSs as do most eukaryotic proteins in this family. The SWEET family is large and diverse. These semisweet proteins probably all function as dimeric carriers. The prokaryotic members of this family have been studied and reviewed (Jia et al. 2018).

Arabidopsis SWEETs homo- and heterooligomerize. Xuan et al., (2013) examined mutant SWEET variants for negative dominance to test if oligomerization is necessary for function. Mutation of the conserved Y57 or G58 residues in SWEET1 led to loss of activity. Coexpression of the defective mutants with functional A. thaliana SWEET1 inhibited glucose transport, indicating that homooligomerization is necessary for function. Collectively, these data imply that the basic unit of SWEETs, is a 3-TMS unit and that a functional transporter contains at least four such domains. The radish (Rs)SWEET genes play vital roles in reproductive organ development (Liu et al. 2023).

Plant SWEETs play crucial roles in cellular sugar efflux processes: phloem loading, pollen nutrition and nectar secretion. Bacterial SemiSWEETs often consist of a triple-helix bundle and form semi-symmetrical, parallel dimers, thereby generating the translocation pathway. Two SemiSWEET isoforms have been crystallized, one in an apparently open state and one in an occluded state, indicating that SemiSWEETs and SWEETs are transporters that undergo rocking-type movements during the transport cycle (Xu et al., 2014). In SemiSWEETs and SWEETs, two triple-helix bundles are arranged in a parallel configuration to produce the 6- and (3 + 1 + 3) -transmembrane-helix pores, respectively. Given the similarity of SemiSWEETs and SWEETs to PQ-loop amino acid transporters and to mitochondrial pyruvate carriers (MPCs), the structures characterized by Xu et al., 2014 may also be relevant to other transporters in the TOG superfamily (Yee et al. 2013). Characterization and expression profiling of the 30 SWEET proteins (8 with one repeat unit, 21 with two, and 1 with 4) in cabbage (Brassica oleracea) revealed their roles in chilling and clubroot disease responses.

Latorraca et al. 2017; captured the translocationprocess by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure  spontaneously adopts occluded and inward-open conformations matching crystal structures. Mutagenesis experiments validated simulation predictions suggesting that state transitions are driven by favorable interactions formed upon closure of extracellular and intracellular 'gates' and by an unfavorable transmembrane helix configuration when both gates are closed. This mechanism leads to tight allosteric coupling between gates, preventing them from opening simultaneously. The substrate appears to take a 'free ride' across the membrane without causing major structural rearrangements in the transporter.

Plant SWEET sugar transporters play roles in phloem transport, nectar secretion, pollen nutrition, stress tolerance, and plant-pathogen interactions (Gao et al. 2017). Fify nine family members have been identified in wheat.  Phylogenetic relationships, numbers of TMSs, gene structures, and motifs showed that TaSWEETs have 3-7 TMSs fall into four clades with 10 different types of motifs. Examination of the expression patterns of 18 SWEET genes revealed that a few are tissue-specific while most are ubiquitously expressed. Using a stem rust-susceptible cultivar, 'Little Club' (LC) the expression of five SWEETs tested induced following inoculation (Gao et al. 2017). Sugar is transported via SWEETS and semi-SWEETS from the extracellular side (via an outward-open state) to the intracellular side (inward-open state) through an intermediate occluded state with both extracellular and intracellular gates closed (Bera and Klauda 2018).

SWEET transporters play roles in phloem loading, seed and fruit development, pollen development, and stress response in plants. Longan (Dimocarpus longan), a subtropic fruit tree with high economic value, is sensitive to cold. A total of 20 longan SWEET (DlSWEET) genes were identified, and their phylogenetic relationships, gene structures, cis-acting elements, and tissue-specific expression patterns were systematically analyzed (Fang et al. 2022). This family is divided into four clades. Gene structure and motif analyses indicated that the majority of DlSWEETs in each clade share similar exon-intron organization and conserved motifs. Tissue-specific gene expression suggested diverse possible functions for DlSWEET genes. DlSWEET1 responds to cold stress, and the overexpression of DlSWEET1 improved cold tolerance in transgenic Arabidopsis, suggesting that DlSWEET1 might play a positive role in D. longan's responses to cold stress (Fang et al. 2022).

The SWEET family is a member of the TOG superfamily, which is believed to have arisen via the pathway:

2 TMSs --> 4 TMSs --> 8 TMSs --> 7 TMSs --> 3 + 3 TMSs (Shlykov et al. 2012; Yee et al. 2013).

The generalized reation catalyzed by known proteins of this family is:

sugars (in) ⇌ sugars (out)

This family belongs to the Transporter-Opsin-G protein-coupled receptor (TOG) Superfamily.



Bera, I. and J.B. Klauda. (2018). Structural Events in a Bacterial Uniporter Leading to Translocation of Glucose to the Cytosol. J. Mol. Biol. 430: 3337-3352.

Cao, Y., W. Liu, Q. Zhao, H. Long, Z. Li, M. Liu, X. Zhou, and L. Zhang. (2019). Integrative analysis reveals evolutionary patterns and potential functions of SWEET transporters in Euphorbiaceae. Int J Biol Macromol 139: 1-11.

Chen, L.Q., B.H. Hou, S. Lalonde, H. Takanaga, M.L. Hartung, X.Q. Qu, W.J. Guo, J.G. Kim, W. Underwood, B. Chaudhuri, D. Chermak, G. Antony, F.F. White, S.C. Somerville, M.B. Mudgett, and W.B. Frommer. (2010). Sugar transporters for intercellular exchange and nutrition of pathogens. Nature 468: 527-532.

Chen, L.Q., X.Q. Qu, B.H. Hou, D. Sosso, S. Osorio, A.R. Fernie, and W.B. Frommer. (2012). Sucrose efflux mediated by SWEET proteins as a key step for phloem transport. Science 335: 207-211.

Chu, Z., B. Fu, H. Yang, C. Xu, Z. Li, A. Sanchez, Y.J. Park, J.L. Bennetzen, Q. Zhang, and S. Wang. (2006). Targeting xa13, a recessive gene for bacterial blight resistance in rice. Theor Appl Genet 112: 455-461.

Eom, J.S., L.Q. Chen, D. Sosso, B.T. Julius, I.W. Lin, X.Q. Qu, D.M. Braun, and W.B. Frommer. (2015). SWEETs, transporters for intracellular and intercellular sugar translocation. Curr. Opin. Plant Biol. 25: 53-62.

Fang, T., Y. Rao, M. Wang, Y. Li, Y. Liu, P. Xiong, and L. Zeng. (2022). Characterization of the Gene Family in Longan () and the Role of in Cold Tolerance. Int J Mol Sci 23:.

Fatima, U., D. Balasubramaniam, W.A. Khan, M. Kandpal, J. Vadassery, A. Arockiasamy, and M. Senthil-Kumar. (2023). AtSWEET11 and AtSWEET12 transporters function in tandem to modulate sugar flux in plants. Plant Direct 7: e481.

Feng CY., Han JX., Han XX. and Jiang J. (2015). Genome-wide identification, phylogeny, and expression analysis of the SWEET gene family in tomato. Gene. 573(2):261-72.

Ferrada, E. and G. Superti-Furga. (2022). A structure and evolutionary-based classification of solute carriers. iScience 25: 105096.

Filyushin, M.A., O.K. Anisimova, A.V. Shchennikova, and E.Z. Kochieva. (2023). Genome-Wide Identification, Expression, and Response to Infection of the Gene Family in Garlic ( L.). Int J Mol Sci 24:.

Gao, Y., Z.Y. Wang, V. Kumar, X.F. Xu, P. Yuan, X.F. Zhu, T.Y. Li, B.L. Jia, and Y.H. Xuan. (2017). Genome-wide identification of the SWEET gene family in wheat. Gene. [Epub: Ahead of Print]

Ge, Y.X., G.C. Angenent, P.E. Wittich, J. Peters, J. Franken, M. Busscher, L.M. Zhang, E. Dahlhaus, M.M. Kater, G.J. Wullems, and T. Creemers-Molenaar. (2000). NEC1, a novel gene, highly expressed in nectary tissue of Petunia hybrida. Plant J. 24: 725-734.

Guan, Y.F., X.Y. Huang, J. Zhu, J.F. Gao, H.X. Zhang, and Z.N. Yang. (2008). RUPTURED POLLEN GRAIN1, a member of the MtN3/saliva gene family, is crucial for exine pattern formation and cell integrity of microspores in Arabidopsis. Plant Physiol. 147: 852-863.

Gupta, A. and R. Sankararamakrishnan. (2018). dbSWEET: An Integrated Resource for SWEET Superfamily to Understand, Analyze and Predict the Function of Sugar Transporters in Prokaryotes and Eukaryotes. J. Mol. Biol. [Epub: Ahead of Print]

Hamada, M., S. Wada, K. Kobayashi, and N. Satoh. (2005). Ci-Rga, a gene encoding an MtN3/saliva family transmembrane protein, is essential for tissue differentiation during embryogenesis of the ascidian Ciona intestinalis. Differentiation 73: 364-376.

Hamada, M., S. Wada, K. Kobayashi, and N. Satoh. (2007). Novel genes involved in Ciona intestinalis embryogenesis: characterization of gene knockdown embryos. Dev Dyn 236: 1820-1831.

Hao, L., X. Shi, S. Qin, J. Dong, H. Shi, Y. Wang, and Y. Zhang. (2023). Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale. BMC Genomics 24: 378.

Hu, B., H. Wu, W. Huang, J. Song, Y. Zhou, and Y. Lin. (2019). Gene Family in : Genome-Wide Identification, Expression and Substrate Specificity Analysis. Plants (Basel) 8:.

Jeena, G.S., S. Kumar, and R.K. Shukla. (2019). Structure, evolution and diverse physiological roles of SWEET sugar transporters in plants. Plant Mol. Biol. 100: 351-365.

Jia, B., L. Hao, Y.H. Xuan, and C.O. Jeon. (2018). New Insight Into the Diversity of SemiSWEET Sugar Transporters and the Homologs in Prokaryotes. Front Genet 9: 180.

Jia, B., X.F. Zhu, Z.J. Pu, Y.X. Duan, L.J. Hao, J. Zhang, L.Q. Chen, C.O. Jeon, and Y.H. Xuan. (2017). Integrative View of the Diversity and Evolution of SWEET and SemiSWEET Sugar Transporters. Front Plant Sci 8: 2178.

Jiang, L., C. Song, X. Zhu, and J. Yang. (2021). SWEET Transporters and the Potential Functions of These Sequences in Tea (). Front Genet 12: 655843.

Jiang, R., L. Wu, J. Zeng, K. Shah, R. Zhang, G. Hu, Y. Qin, and Z. Zhang. (2023). Identification of Family in Pitaya () and Key Roles of and in Sugar Accumulation. Int J Mol Sci 24:.

Kanno, Y., T. Oikawa, Y. Chiba, Y. Ishimaru, T. Shimizu, N. Sano, T. Koshiba, Y. Kamiya, M. Ueda, and M. Seo. (2016). AtSWEET13 and AtSWEET14 regulate gibberellin-mediated physiological processes. Nat Commun 7: 13245.

Kuanyshev, N., A. Deewan, S.S. Jagtap, J. Liu, B. Selvam, L.Q. Chen, D. Shukla, C.V. Rao, and Y.S. Jin. (2021). Identification and analysis of sugar transporters capable of co-transporting glucose and xylose simultaneously. Biotechnol J e2100238. [Epub: Ahead of Print]

Kumawat, S., Y. Sharma, S. Vats, S. Sudhakaran, S. Sharma, R. Mandlik, G. Raturi, V. Kumar, N. Rana, A. Kumar, H. Sonah, and R. Deshmukh. (2022). Understanding the role of SWEET genes in fruit development and abiotic stress in pomegranate (Punica granatum L.). Mol Biol Rep 49: 1329-1339.

Latorraca, N.R., N.M. Fastman, A.J. Venkatakrishnan, W.B. Frommer, R.O. Dror, and L. Feng. (2017). Mechanism of Substrate Translocation in an Alternating Access Transporter. Cell 169: 96-107.e12.

Lee, Y., T. Nishizawa, K. Yamashita, R. Ishitani, and O. Nureki. (2015). Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter. Nat Commun 6: 6112.

Liu, N., Z. Wei, X. Min, L. Yang, Y. Zhang, J. Li, and Y. Yang. (2023). Genome-Wide Identification and Expression Analysis of the Gene Family in Annual Alfalfa (). Plants (Basel) 12:.

Liu, T., Q. Cui, Q. Ban, L. Zhou, Y. Yuan, A. Zhang, Q. Wang, and C. Wang. (2023). Identification and expression analysis of the SWEET genes in radish reveal their potential functions in reproductive organ development. Mol Biol Rep. [Epub: Ahead of Print]

Shlykov, M.A., W.H. Zheng, J.S. Chen, and M.H. Saier, Jr. (2012). Bioinformatic characterization of the 4-Toluene Sulfonate Uptake Permease (TSUP) family of transmembrane proteins. Biochim. Biophys. Acta. 1818: 703-717.

Takanaga, H. and W.B. Frommer. (2010). Facilitative plasma membrane transporters function during ER transit. FASEB J. 24: 2849-2858.

Tao, Y., L.S. Cheung, S. Li, J.S. Eom, L.Q. Chen, Y. Xu, K. Perry, W.B. Frommer, and L. Feng. (2015). Structure of a eukaryotic SWEET transporter in a homotrimeric complex. Nature 527: 259-263.

Wang, L., L. Yao, X. Hao, N. Li, W. Qian, C. Yue, C. Ding, J. Zeng, Y. Yang, and X. Wang. (2018). Tea plant SWEET transporters: expression profiling, sugar transport, and the involvement of CsSWEET16 in modifying cold tolerance in Arabidopsis. Plant Mol. Biol. 96: 577-592.

Wu, Z., K.M. Soliman, J.J. Bolton, S. Saha, and J.N. Jenkins. (2008). Identification of differentially expressed genes associated with cotton fiber development in a chromosomal substitution line (CS-B22sh). Funct Integr Genomics 8: 165-174.

Xie, H., D. Wang, Y. Qin, A. Ma, J. Fu, Y. Qin, G. Hu, and J. Zhao. (2019). Genome-wide identification and expression analysis of SWEET gene family in Litchi chinensis reveal the involvement of LcSWEET2a/3b in early seed development. BMC Plant Biol 19: 499.

Xu Y., Tao Y., Cheung LS., Fan C., Chen LQ., Xu S., Perry K., Frommer WB. and Feng L. (2014). Structures of bacterial homologues of SWEET transporters in two distinct conformations. Nature. 515(7527):448-52.

Xuan, Y.H., Y.B. Hu, L.Q. Chen, D. Sosso, D.C. Ducat, B.H. Hou, and W.B. Frommer. (2013). Functional role of oligomerization for bacterial and plant SWEET sugar transporter family. Proc. Natl. Acad. Sci. USA 110: E3685-3694.

Yang, B., A. Sugio, and F.F. White. (2006). Os8N3 is a host disease-susceptibility gene for bacterial blight of rice. Proc. Natl. Acad. Sci. USA 103: 10503-10508.

Yee, D.C., M.A. Shlykov, A. Västermark, V.S. Reddy, S. Arora, E.I. Sun, and M.H. Saier, Jr. (2013). The transporter-opsin-G protein-coupled receptor (TOG) superfamily. FEBS J. 280: 5780-5800.

Zhang, G., S.S. Liu, X.J. Yang, Y. Chen, L.L. Liu, and S.X. Guo. (2016). [Molecular cloning and characterization of a novel DoSWEET1 gene from Dendrobium officinale]. Yao Xue Xue Bao 51: 991-997.

Zhang, R., K. Niu, and H. Ma. (2020). Identification and Expression Analysis of the Gene Family from Under Abiotic Stresses. DNA Cell Biol 39: 1606-1620.

Zhu, L.Q., Z.K. Bao, W.W. Hu, J. Lin, Q. Yang, and Q.H. Yu. (2015). Cloning and functional analysis of goat SWEET1. Genet Mol Res 14: 17124-17133.


TC#NameOrganismal TypeExample

Alfalfa Nodulin MtN3


MtN3 of Medicago truncatula (P93332)


Golgi/E.R. Sweet1 glucose/galactose facilitator (Km ≥ 50mM) (Chen et al. 2010)


Sweet1 of Caenorhabditis elegans (O45102)


The sea squirt sugar transporter, Rga or Sweet1; required for normal development (Hamada et al., 2007; Chen et al., 2010).


Rga of Ciona intestinalis (F6U696)

2.A.123.1.12Sugar transporter SWEET1 (Protein saliva)Animals

Slv of Drosophila melanogaster


Bidirectional sugar (sucrose) transporter SWEET11 (AtSWEET11).  Oligomerization, probably to the dimeric form, has been demonstrated (Xuan et al. 2013). Important for phloem loading.


SWEET11 of Arabidopsis thaliana

2.A.123.1.14Sugar transporter SWEET1Amoebaslc50a1 of Dictyostelium discoideum

SWEET homologue of 375 aas and 7 TMSs in a 3 + 4 arrangement.

Stramenopiles (Marine diatom)

SWEET homologue of Phaeodactylum tricornutum


Uncharacterized protein of 262 aas and 7 TMSs

Rhodophyta (Algae)

UP of Galdieria sulphuraria (Red alga)


MtN3-like protein of 686 aas and 7-8 TMSs, 1 N-terminal and 7 between residues 380 and 590.


MtN3-like protein of Plasmodium falciparum


SWEET2b sugar transporter. Sequesters sugars in root vacuoles.  The 3-d structure is known. The subunit consists of two asymetic triple helix bundles (TMSs 1-3 and 5-7) connected by TMS4. SWEET2b is in an apparent inward (cytosolic) open state forming homomeric trimers. TMS4 tightly interacts with the first triple-helix bundle within a protomer and mediates key contacts among protomers (Tao et al. 2015).

SWEET2b of Oryza sativa


Sweet1 (SLC50A1).  99.6% identical to the goat (Capra hircus) mammary gland epithelial homologue which has been characterized (Zhu et al. 2015).

Sweet1 of Ovis aries (sheep)


Sweet family member of 305 aas and 7 TMSs.  Mediates both low-affinity uptake and efflux of sugars across the membrane. (Wu et al., 2008)


Sweet of Citrus clementina


Uncharacterized protein of 197 aas and 7 TMSs

UP of Acidimicrobium sp. BACL27


Uncharacterized duplicated protein of 709 aas and 15 TMSs in a 7 + 7 + 1 arrangement. The protein contains two 7 TMS Sweet domains followed by an Atrophin-1 domain. There is no close homologue in the NCBI database, suggesting that it could be a result of a sequencing artifact.

UP of Ananas comosus


Uncharacterized protein of 1089 aas and 28 TMSs in a 7 + 7 + 7 + 7 arrangement.

UP of Phytophthora ramorum (Sudden oak death agent)


Vacuolar hexose (fructose) transporter of 230 aas and 7 TMSs, Sweet16 (Eom et al. 2015). It plays an iimportant role in cold tolerance (Wang et al. 2018).

Sweet16 of Arabidopsis thaliana (Mouse-ear cress)


Sweet9 of 258 aas and 7 TMSs.  Important for nectar secretion (Eom et al. 2015).

Sweet9 of Arabidopsis thaliana (Mouse-ear cress)


Sweet family member of 89 aas and 3 TMSs.  Associated with a trehalose phosphatase, possibly suggesting al role in trehalose transport.

Semi-sweet of Methanobacterium lacus


Sweet13 (Sweet12) of 294 aas and 7 TMSs.  Transports the plant hormone, gibberellin (GA).  Sweet14 also transports gibberellin.  A double mutant has a defect in anther dehiscence. This mutant also exhibits altered long distant transport of exogenously applied GA and altered responses to GA during germination and seedling stages (Kanno et al. 2016).  In dragon fruit (pitaya; H. undatus) Sweets function in phloem loading, seed filling, nectar secretion, and fruit sweetness development (Jiang et al. 2023).

SWEET13 of Arabidopsis thaliana (Mouse-ear cress)


SWEET transporter 1 of 262 aas and 7 TMSs. Plays a role in the D. officinale symbiotic germination process (Zhang et al. 2016). This organism provides a traditional chinese medicine. There are 25 SWEET genes in this organism (Hao et al. 2023). Most have 7 TMSs and contain two conserved MtN3/saliva domains. They were divided into four clades, and are found in various tissues. Sixteen were significantly regulated under cold, drought, and MeJA treatment (Hao et al. 2023).

Sweet transporter of Dendrobium officinale


Bidirectional sugar transporter, SWEET2a, of 2243 aas and 7 TMSs.  It mediates both low-affinity uptake and efflux of sugars across the plasma membrane and plays a role in early seed development in Litchi chinensis (Xie et al. 2019).

SWEET2a of Oryza sativa subsp. japonica (Rice)


Bidirectional sugar transporter SWEET3b of 2252 aas and 7 TMSs.  It mediates both low-affinity uptake and efflux of sugars across the plasma membrane and plays a role in early seed development in Litchi chinensis (Xie et al. 2019).

SWEET3b of Oryza sativa subsp. japonica (Rice)


Senescence-associated protein 29, SAG29 (SWEET15)


SAG29 of Arabidopsis thaliana (Q9FY94)


Bidirectional sugar transporter SWEET7, of 258 aas and 7 TMSs. It mediates both low-affinity uptake and efflux of sugar across the plasma membrane. AtSWEET7 transports glucose and xylose simultaneously with no inhibition (Kuanyshev et al. 2021).


SWEET7 of Arabidopsis thaliana (Mouse-ear cress)


Stromal cell protein (SCP) homologue, HsSWEET1 or RAG1AP1. Transports glucose and galactose bidirectionally. Present in the ER, Golgi and plasma membrane (Chen et al., 2010).


SLC50A1 of Homo sapiens


Ruptured pollen Grain-1, Sweet8 or Nodulin MtN3 family protein (essential for pollen viability). (Guan et al., 2008; Chen et al. 2010).


RPGI of Arabidoposis thaliana (Q8LFH5)


Host disease susceptible protein, Xa13 or Os8N3, for bacterial blight (Yang et al., 2006; Chu et al., 2006). Bidirectional sugar transporter, Sweet 11 (Chen et al., 2010)


Oryza sativa (Q6YZF3)


Nec1; predominantly expressed in nectaries; involved in sugar metabolism and nectar secretion (Ge et al., 2000)


Nec1 of Petunia hybrida (Q9FPN0)


Rga (Recombination-activating gene 1) (Hamada et al., 2005)


Rga of Mus musculus (Q9CXK4)


Sweet1: bidirectional low affinity glucose uniporter, Km = ~9 mM (Does not transport mannose, fructose or galactose) (Chen et al. 2010). The structure is know, and three regions, each containing several well conserved essential residues, comprise the substrate-binding pocket, the extrafacial gate, and the intrafacial gate (Xuan et al. 2013; Tao et al. 2015).  The orthologous SWEET1 in Camellia sinensis (tea) transports glucose, glucose analogues, and other hexoses (Wang et al. 2018).


Sweet1 of Arabidopsis thalinana (Q8L9J7)


TC#NameOrganismal TypeExample

The 7 TMS (242aa) bacterial MtN3 homologue


MtN3 homologue of Mycoplasma arthritidis (B3PMT4)


SWEET homologue of 125 aas and 3 TMSs; resembles 2.A.123.2.3 with all 3 TMSs overlapping.

SWEET homologue of Phytophthora sojae (Soybean stem and root rot agent) (Phytophthora megasperma f. sp. glycines)


SWEET homologue of 125 aas and 3 TMSs.  Closely related to 2.A.123.2.10.

SWEET homologue of Phytophthora parasitica


SWEET homologue of 84 aas and 3 TMSs

SWEET homologue of Methanocella conradii


Uncharacterized protein of 728 aas and 5 putative TMSs with 4 N-terminal TMSs, where the first 3 are homologous to semisweets of 3 TMSs. The long sequence with one large centrally located peak of hydrophobicity includes several recognized protein domains following the SWEET domain in the following order:  Cache-3 - Cache-1 - dimerization interface domain - HAMP domain - followed by two PAS domains.  Another protein (UniProt acc #I3IJJ5 of 762 aas), has residues 3 - 635 aas) showing 83% sequence identity with residues 96 - 728 in 2.A.123.2.13.

UP of Candidatus Jettenia caeni


SemiSWEET of 86 aas and 3 TMSs specific for sucrose. The basic unit of SWEETs may be a 3-TMS unit, and it has been suggested that a functional transporter contains at least four such domains, although this suggestion has not been substantiated (Xuan et al. 2013).

SemiSWEET of Bradyrhizobium diazoefficiens


Putative uncharacterized protein of 99 aas and 3 TMSs

Hypothetical protein UW38 of Candidatus Saccharibacteria bacterium


Facilitated glucose/sucrose/sugar/monoolein transporter of 89 aas and 3 TMSs. The homodimer mediates transmembrane sugar transport down a concentration gradient. Transport is probably effected by rocking-type movements, where a cargo-binding cavity opens first on one and then on the other side of the membrane (Lee et al. 2015).

Semisweet sugar transporter of E. coli


3 TMS MtN3 homologue (85aas)


MtN3 of MtN3 of Prochlorococcus marinus (A2BS89)


Half sized (3 TMS) bacterial MtN3 protein homologue (85aas)


MtN3 homologue of Fusobacterium mortiferum (C3WG44)


3 TMS bacterial MtN3 homologue (96aas)


MtN3 homologue of Leptospira interrogans (Q8F4F7)


3 TMS Sweet homologue, MJ_0110 (93aas)


MJ_0110 of Methanocaldococcus jannashii (Q57574)


SemiSWEET half glucose transporter of 93 aas and 3 TMSs with an N-terminal amphipathic α-helix.  The protein occurs as a tight homodimer with the translocation channel between the two monomers.  The 3-d structure is known at 2.4 Å resolution revealing the outward open conformation (Xu et al. 2014). The occluded state of the Vibrio sp. N418 SemiSWEET (9.A.58.3.1) has been solved at 1.7 Å resolution (Xu et al. 2014).  The presence of these two states argues in favor of a carrier (rocker switch) mechanism rather than a channel-type mechanism (Xu et al. 2014).


SemiSWEET of Leptospira biflexa


SemiSWEET homologue of 89 aas and 3 TMSs


SemiSWEET of Rickettsia bellii


SWEET homologue of 141 aas and 4 putative TMSs.

SWEET homologue of Anabaena variabilis


SWEET homologue of 231 aas and 7 TMSs

SWEET homologue of Mycoplasma hyopneumoniae


TC#NameOrganismal TypeExample

SemiSWEET half putative sugar transporter of 97 aas and 3 TMSs with an N-terminal amphipathic α-helix.  The protein occurs as a tight homodimer with the translocation channel between the two monomers.  The 3-d structure is known at 1.7 Å resolution revealing the occluded conformation (Xu et al. 2014). The outward open state of the Leptospira biflexa SemiSWEET (2.a.123.2.6) has been solved at 2.4 Å resolution (Xu et al. 2014).  The presence of these two states argues in favor of a carrier (rocker switch) mechanism rather than a channel-type mechanism (Xu et al. 2014).


SemiSWEET of Vibrio sp. N418


Uncharacterized protein of 107 aas.


UP of Rhodobacteraceae bacterium KLH11


Uncharacterized conserved protein of 273 aas and 7 TMSs containing PQ loop repeats.

UP of Geodermatophilus obscurus


Uncharacterized protein of 97 aas and 3 TMSs.

UP of Photobacterium leiognathi


TC#NameOrganismal TypeExample

Membrane protein of 209 aas and 7 TMSs with a putative N-terminal lipid A disaccharide synthase domain.  This protein is a member of the "Lipid A Biosynthesis, N-terminal (LAB_N) domain in Pfam/CDD, related to the SWEET family.


Membrane protein of Gramella forsetii


Uncharacterized protein of 115 aas and 3 TMSs.


UP of Frateuria aurantia (Acetobacter aurantius)


Uncharacterized protein (putative lipid A synthesis protein domain) of 115 aas and 3 TMSs.


UP of Stenotrophomonas maltophilia (Pseudomonas maltophilia) (Xanthomonas maltophilia)


TC#NameOrganismal TypeExample

Uncharacterized protein of 208 aas and 2 N-terminal TMSs.

UP of Balneolaceae bacterium (soda lake metagenome)


Uncharacterized protein of 207 aas and 2 or 3 N-terminal TMSs

UP of Serinicoccus sediminis


Uncharacterized protein of 204 aas and 3 N-terminal TMSs followed by a large hydrophilic domain, characteristic of this subfamily (TC# 2.A.123.5).

UP of Janibacter terrae (hydrocarbon metagenome)


Uncharacterized protein of 210 aas and 3 N-terminal TMSs.

UP of Chitinophagaceae bacterium (ecological metagenome)


Uncharacterized protein of 207 aas and 3 or more TMSs

UP of Methanohalobium evestigatum